Morphologically structured model for antitumoral retamycin production during batch and fed‐batch cultivations of <i>Streptomyces olindensis</i>

Giudici, Reinaldo; Pamboukian, Celso Ricardo Denser; Facciotti, Maria Cândida Reginato

doi:10.1002/bit.20055

Cited by 17 publications

(13 citation statements)

References 30 publications

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“…Although all cells in a hyphal element share a common cytoplasm with multiple nuclei, significant cellular and functional differentiation within the mycelial pellet exists (Megee et al 1970). Earlier studies indicate that secondary metabolite production in filamentous organisms is associated with this morphological differentiation, which favors a structured approach to modeling (Giudici et al 2004; Manteca et al 2008). In creating a structured model, hyphae may be divided into three compartments: (i) apical, (ii) subapical, and (iii) hyphal compartment, each type indicating a different stage of cellular differentiation (Fig.…”

Section: Mathematical Model Descriptionmentioning

confidence: 99%

“…Recent structured models correlate the amount of antibiotic production in a fermentation to the amount of subapical or hyphal compartments, where secondary metabolite formation is expected to take place (Paul and Thomas 1996; Birol et al 2002; Giudici et al 2004; Liu et al 2005). The ratio of component types can be followed over pellet development, or alternatively, represented as a function of pellet radius.…”

Section: Model Outputmentioning

confidence: 99%

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Structured morphological modeling as a framework for rational strain design of Streptomyces species

Celler

Picioreanu

Loosdrecht

et al. 2012

Antonie van Leeuwenhoek

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Successful application of a computational model for rational design of industrial Streptomyces exploitation requires a better understanding of the relationship between morphology—dictated by microbial growth, branching, fragmentation and adhesion—and product formation. Here we review the state-of-the-art in modeling of growth and product formation by filamentous microorganisms and expand on existing models by combining a morphological and structural approach to realistically model and visualize a three-dimensional pellet. The objective is to provide a framework to study the effect of morphology and structure on natural product and enzyme formation and yield. Growth and development of the pellet occur via the processes of apical extension, branching and cross-wall formation. Oxygen is taken to be the limiting component, with the oxygen concentration at the tips regulating growth kinetics and the oxygen profile within the pellet affecting the probability of branching. Biological information regarding the processes of differentiation and branching in liquid cultures of the model organism Streptomyces coelicolor has been implemented. The model can be extended based on information gained in fermentation trials for different production strains, with the aim to provide a test drive for the fermentation process and to pre-assess the effect of different variables on productivity. This should aid in improving Streptomyces as a production platform in industrial biotechnology. Electronic supplementary material The online version of this article (doi:10.1007/s10482-012-9760-9) contains supplementary material, which is available to authorized users.

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Section: Mathematical Model Descriptionmentioning

confidence: 99%

Section: Model Outputmentioning

confidence: 99%

Structured morphological modeling as a framework for rational strain design of Streptomyces species

Celler

Picioreanu

Loosdrecht

et al. 2012

Antonie van Leeuwenhoek

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“…In their model assumptions, the apical compartment was responsible for hyphal extension, and the subapical compartment branched to form new apical compartment, which was a good approach to experimental observations, for branching seldom occurs in the rear part of the hypha. The Nielsen model was further applied in simulation of penicillin fermentation and retamycin fermentation with good agreement (Zangirolami et al 1998;Birol et al 2002;Giudici et al 2004). Based on the quantitative measurement of morphological differentiation with an image analytical system, Paul & Thomas (1996) incorporated hyphal differentiation into the morphologically structured model for penicillin fermentation process.…”

mentioning

confidence: 99%

A Population-Based Morphologically Structured Model for Hyphal Growth and Product Formation in Streptomycin Fermentation

Liu

Xing

Han

2005

World J Microbiol Biotechnol

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A population model discriminating the hyphae according to the hyphal length and a morphologically structured model considering the specific function of different morphological forms of a hypha are combined together to describe mycelial growth, substrate consumption and secondary metabolite formation in streptomycin fermentation. In the population model, the growth modes of hyphae with different age or length are considered, while in the morphologically structured model, the morphological forms of hyphae and their functions in growth and metabolism are described. The population model and the morphologically structured model are interrelated by a branching function and a differentiation function. In the model, the growth rate of immature apical compartment is distinguished from those of matured ones, branching is proposed to occur only in the subapical region, and the hyphal compartment is assumed to synthesize secondary metabolites. The model is successfully applied to simulate the batch fermentation process of streptomycin production. The growth characteristics of filamentous microorganisms are also discussed using the model predictions.

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“…Hence, these conditions seem to be strain dependent. For instance, in Streptomyces olidensis (retamycin) [32], Streptomyces tendae (nikkomycins) [33], Streptomyces lividans (hybrid antibiotics) [34] and Streptomyces coelicolor (Undecylprodigiosin, Actinorhodin) [30], pellet formation is essential for good production. However, in Streptomyces noursei (nystatin) [35] and Streptomyces fradiae (tylosin) [36], formation of pellets leads to worse antibiotic production than disaggregated growth.…”

Section: Correlation Between Streptomyces Life Cycle and Antibiotic Pmentioning

confidence: 99%

Streptomyces as a Source of Antimicrobials: Novel Approaches to Activate Cryptic Secondary Metabolite Pathways

Manteca¹,

Yagüe²

2019

Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods

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Streptomyces is the most important bacterial genus for bioactive compound production. These soil bacteria are characterized by a complex differentiation cycle. Streptomyces is extremely important in biotechnology, producing approximately two thirds of all antibiotics, as well as many compounds of medical and agricultural interest. Drug discovery from streptomycetes became challenging once the most common compounds were discovered, and the system was basically abandoned by industry. Simultaneously, antibiotic resistance is increasing dramatically, and new antibiotics are required. Screening from nature is being resumed (exploring new environments, looking for elicitors, metagenome, etc.). Secondary metabolism is conditioned by differentiation; although the relationship between both has long remained elusive, differentiation as a trigger for antibiotic production remains basically unexplored. Most cultures used in screening campaigns for new bioactive molecules have been performed empirically, and workflow was extremely productive during the so-called golden age of antibiotics; however, currently there is a bottleneck. Streptomyces is still the most important natural source of antibiotics, and it also harbors many cryptic secondary metabolite pathways not expressed under laboratory conditions. In this chapter, we review strategies based on differentiation, one of the keys improving secondary metabolite production and activating cryptic pathways to face the challenges of drug discovery.

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Morphologically structured model for antitumoral retamycin production during batch and fed‐batch cultivations of Streptomyces olindensis

Cited by 17 publications

References 30 publications

Structured morphological modeling as a framework for rational strain design of Streptomyces species

Structured morphological modeling as a framework for rational strain design of Streptomyces species

A Population-Based Morphologically Structured Model for Hyphal Growth and Product Formation in Streptomycin Fermentation

Streptomyces as a Source of Antimicrobials: Novel Approaches to Activate Cryptic Secondary Metabolite Pathways

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